6-ketoprostaglandin-f1-alpha and Heart-Diseases

To reveal changes in the thromboxane-prostacyclin balance and platelet aggregability in patients with various variants of minor cardiac abnormalities.. Six-five patients (mean age 23.0 +/- 0.7 years) with minor cardiac abnormalities and 10 apparently healthy individuals were examined. Platelet aggregation induced by adrenaline, adenosine diphosphate, collagen) and the plasma levels of thromboxane B2 (TxB) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha) were determined.. Patients with abnormally located chordae (ALC) were found to have no deviations in the thromboxane-prostacyclin balance and platelet aggregability. Only decreased collagen aggregation was recorded in the groups of first-degree mitral prolapse (MP) and first-degree MP + ALC; in second-degree MP and second-degree MP + ALC, there was a reduction in platelet aggregation on all inductors and an increase in TxB2. Patients with myxomatous degeneration of the mitral valve exhibited reduced collagen-induced platelet aggregation and lower plasma 6-keto-PGF1alpha levels.. The most pronounced changes in the thromboxane-prostacyclin balance and platelet aggregability were found in patients with MP and second-degree regurgitation, three intracardiac micro-abnormalities, and myxomatous degeneration of the mitral valve.

Topics: 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Adolescent; Adult; Blood Platelets; Case-Control Studies; Collagen; Epinephrine; Female; Heart Diseases; Hemostasis; Humans; Male; Platelet Aggregation; Severity of Illness Index; Thromboxane B2; Ultrasonography; Young Adult

Because thromboxane A2 is implicated in the pathophysiology of acute lung injury, the aim of this study was to evaluate the effects of selective thromboxane A2 synthase inhibition on cardiopulmonary function in the experimental setting of severe smoke inhalation injury.. Sixteen adult sheep were operatively instrumented for chronic study. The injured intervention group was treated with the selective thromboxane A2 synthase inhibitor OKY-046, whereas the injured control group received only the vehicle (n = 8 each).. The progressive increase in thromboxane B2 lung lymph concentrations in control animals was associated with increased transvascular fluid flux, augmented resistances in the pulmonary and systemic circulation, and a reciprocal decrease in cardiac output. In addition, end-systolic pressure-diameter relation and maximum +dp/dt were markedly depressed as compared with baseline (24 h: 14.3 +/- 0.9 vs. 8.9 +/- 0.5 mmHg/mm and 2,120 +/- 50 vs. 1,915 +/- 40 mmHg/s, respectively; each P < 0.05). Infusion of OKY-046 significantly inhibited pulmonary thromboxane B2 delivery, attenuated the early increase in pulmonary vascular resistance, and blocked the increase in systemic vascular resistance. In addition, OKY-046 blunted and delayed the decrease in cardiac output and maintained end-systolic pressure-diameter relation, +dp/dt, and lung lymph flow at baseline values.. These findings suggest that selective thromboxane A2 synthase inhibition may represent a goal-directed therapeutic approach to alleviate cardiovascular and pulmonary dysfunction in the setting of smoke inhalation injury.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Capillary Permeability; Echocardiography; Enzyme Inhibitors; Heart Diseases; Hemodynamics; Infusions, Intravenous; Lung Diseases; Methacrylates; Pulmonary Circulation; Sheep; Smoke Inhalation Injury; Thromboxane-A Synthase

The experiment was conducted with SD male rats. After they had been each given an intravenous injection of high molecular weight dextran (0.8 ml/100 g body wt) once a day for 4 days, they were brought under the observation of ECG and mesentery microcirculation. Microthrombi were found in the venules and capillaries of each rat of the experimental group, while in the microcirculation of the control group rats, no microthrombi were found. No changes were found in the ECGs of the rats (n = 6) in the control group after the injections, while the rats in the subject group all suffered a rise in the S-T segment of ECG, an indication of myocardial injuries. The rise was significantly in positive correlation to the increase in microthrombi in number (r = 0.944, P < 0.01). The erythrocytes of the rats in the subject group clustered to become rouleau-like, and platelets aggregated by tens and hundreds to form microthrombi. Their blood also showed a significant decrease in number of platelets. The degree of platelet aggregation and the scores of the rise on ECG were significantly in positive correlation as shown by the results: y = 20 + 94x, r = 0.94, P < 0.01. The plasma TXB2 of the subject group increased obviously but the change of 6-K-PGF1 alpha in the blood was not significant. The content of plasma TXB2 and the scores that indicated the rise in the S-T segment of the ECG showed significantly a positive correlation by the analysis of linear regression equation: y = 109.997 +/- 116.25x, r = 0.889, P < 0.05. The activity of Na(+)-K(+)-ATPase on the myocardial cell membranes of the rats with microthrombi was significantly reduced as compared with that of the rats in the control group (P < 0.01). The activity of the Na(+)-K(+)-ATPase was significantly in negative correlation to the rise in the S-T segment of ECG (P < 0.05). This study demonstrates that the above changes are the causes of myocardial injuries in rats with circulatory thrombi.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Dextrans; Electrocardiography; Erythrocyte Aggregation; Heart Diseases; Male; Microcirculation; Myocardium; Rats; Sodium-Potassium-Exchanging ATPase; Thrombosis; Thromboxane B2

We evaluated the effect of tumor necrosis factor-alpha (TNF-alpha) and interleukin-1 alpha (IL-1 alpha) on pig cardiopulmonary function by intravenously infusing each cytokine individually or in combination (0.5 microgram/kg from 0 to 0.5 h + 5 ng.kg-1 x min-1 from 0.5 to 6 h for each cytokine). The role of eicosanoids in mediating the TNF-alpha + IL-1 alpha-induced cardiopulmonary dysfunction was also investigated by pretreating cytokine-infused pigs with CGS 8515 (5-lipoxygenase inhibitor) or indomethacin (cyclooxygenase inhibitor). Coinfusion of TNF-alpha with IL-1 alpha caused additive increases (P < 0.05) in total peripheral resistance and plasma concentrations of 6-keto-prostaglandin F1 alpha (PGF1 alpha). The increases in mean pulmonary arterial pressure (Ppa), pulmonary vascular resistance (PVR), alveolar-arterial O2 gradient (AaDO2), alveolar dead space-to-tidal volume ratio (VD/VT), and plasma concentrations of thromboxane B2 were either additive or synergistic. CGS 8515 blocked the TNF-alpha + IL-1 alpha-induced increases (P < 0.05) in mean aortic pressure, total peripheral resistance (4-6 h), VD/VT (5-6 h), and, at 6 h, attenuated the increases in Ppa, PVR, and AaDO2. Indomethacin blocked or attenuated the cytokine-induced increases (P < 0.05) in Ppa, PVR, AaDO2, VD/VT, and plasma concentrations of thromboxane B2 and 6-keto-PGF1 alpha. The 1-to 2-h systemic hypotension, caused by TNF-alpha + IL-1 alpha, was not abrogated by either indomethacin or CGS 8515. The cytokines did not alter plasma concentrations of leukotriene B4 or 5-hydroxyeicosatetraenoic acid. We conclude that coinfusion of TNF-alpha with IL-1 alpha induces physiological responses that are additive or synergistic and that cyclooxygenase and 5-lipoxygenase products (other than leukotriene B4 and 5-hydroxyeicosatetraenoic acid) importantly mediate cardiopulmonary dysfunction in pigs infused with TNF-alpha + IL-1 alpha.

Topics: 6-Ketoprostaglandin F1 alpha; Albumins; Animals; Arachidonic Acids; Bronchoalveolar Lavage Fluid; Chromatography, High Pressure Liquid; Cyclooxygenase Inhibitors; Cytokines; Dinoprost; Drug Synergism; Eicosanoids; Heart; Heart Diseases; Hydroxyeicosatetraenoic Acids; Indomethacin; Injections, Intravenous; Interleukin-1; Leukotriene B4; Lipoxygenase Inhibitors; Lung; Lung Diseases; Naphthoquinones; ortho-Aminobenzoates; Swine; Thromboxane B2; Tumor Necrosis Factor-alpha; Vascular Resistance

The exposure of cardiac cells to OFR generated artificially, showed a marked decrease (p less than 0.01) in cellular utilization of glucose along with a significant decrease in calcium uptake (p less than 0.05). We have also provided evidence for a direct relationship of neutrophil OFR production with the extent of myocardial ischemia in patients of myocardial infarction. Our data provides evidence for implication of OFR in myocardial injury and the pivotal role played by modulators like calcium, ECGF and prostaglandins in potentiating damage to the myocardium.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Animals; Calcium; Coronary Artery Disease; Endothelial Growth Factors; Female; Free Radicals; Glucose; Heart Diseases; Humans; In Vitro Techniques; Indomethacin; Macaca mulatta; Male; Mice; Middle Aged; Myocardium; Oxidation-Reduction; Oxygen; Thromboxane B2

Many organs have the capacity to form prostanoids. Under pathophysiological conditions the biosynthesis of TXB2 and 6-oxo-PGF1 alpha is markedly increased in the myocardium and the gastric mucosa. Tumor growth is linked with an enhanced prostanoid formation. Furthermore a rise of the PG content could be found in the liquor, aqueous humor and urine under diseases of the related organs. These results could be of some significance for diagnosis and therapy control.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Aqueous Humor; Brain Diseases; Child; Gastric Mucosa; Gastritis; Guinea Pigs; Heart Diseases; Humans; Hypertension, Portal; In Vitro Techniques; Indomethacin; Kidney Transplantation; Myocardium; Skin Neoplasms; Thromboxane B2

This study was performed to determine the relationship between plasma concentration of thromboxane B2 (TXB2), 6-keto-prostaglandin F1a and atrial thrombosis in patients with mitral stenosis (MS). By radioimmunoassay and pathological examination, peripheral plasma TXB2 level was remarkably higher in patients with MS and persistent atrial fibrillation (AF) than in patients with MS but without AF (P less than 0.01). Plasma TXB2 level was significantly higher in patients with than in those without atrial thrombosis (P less than 0.05). There was no significant difference in plasma 6-keto-PGF1 alpha, plasma prostanoids level in peripheral venous blood correlated closely with that in left atrial blood. Patients with high plasma TXB2 level had a greater incidence of microthrombosis.

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Adult; Atrial Fibrillation; Female; Heart Diseases; Humans; Male; Middle Aged; Mitral Valve Stenosis; Rheumatic Heart Disease; Thrombosis; Thromboxane B2

Interleukin-2 (IL-2) produces toxicity characterized by generalized edema within 24 hours. This study tests whether the rate of IL-2 administration modulates the onset of edema and examines thromboxane (Tx) and neutrophils as possible mediators of this event. Recombinant human IL-2, 10(5) U (n = 7), 10(6) U (n = 9), or vehicle (n = 8) were given to anesthetized rats intravenously during a period of 1 hour. At 6 hours edema, as measured by increase in wet to dry weight (w/d) ratio, was present in the heart, liver, and kidney, with 10(5) U IL-2 and in the lung, heart, liver and kidney, with 10(6) U IL-2, relative to values with vehicle-infused controls (all p less than 0.05). With a 1-hour infusion of 10(6) U IL-2, there was an increase in plasma thromboxane (Tx)B2 level to 1290 +/- 245 pg/mL, higher than 481 +/- 93 pg/mL in control rats (p less than 0.05); lung polymorphonuclear leukocyte (PMN) sequestration of 53 +/- 7 PMN/10 higher-power fields (HPF) relative to 23 +/- 2 PMN/10 HPF in controls (p less than 0.05); and increased bronchoalveolar lavage (BAL) fluid protein concentration of 1970 +/- 210 micrograms/mL relative to 460 micrograms/mL in controls (p less than 0.05). When 10(6) U IL-2 was given as a 1-minute intravenous bolus (n = 9), edema was not demonstrated, plasma TxB2 levels were similar to controls, there was no leukosequestration, and BAL protein levels were normal. These data indicate that a constant infusion but not the rapid bolus administration of IL-2 produces in rats multiple-system organ edema, increased plasma TxB2, sequestration of PMNs, and microvascular permeability. These findings may explain the early toxicity seen in patients given high-dose IL-2 in cancer treatment.

Topics: 6-Ketoprostaglandin F1 alpha; Animals; Bronchoalveolar Lavage Fluid; Edema; Heart Diseases; Infusions, Intravenous; Injections, Intravenous; Interleukin-2; Kidney Diseases; Liver Diseases; Male; Neutrophils; Pulmonary Edema; Rats; Rats, Inbred Strains; Recombinant Proteins; Thromboxane A2; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Aged, 80 and over; Cerebrovascular Disorders; Dinoprostone; Female; Heart Diseases; Humans; Male; Middle Aged; Radioimmunoassay; SRS-A; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Alprostadil; Arachidonic Acids; Extracorporeal Circulation; Female; Heart Diseases; Humans; Male; Middle Aged; Prostaglandins; Thromboxane B2

Topics: 6-Ketoprostaglandin F1 alpha; Adolescent; Child; Extracorporeal Circulation; Female; Heart Diseases; Hemoglobins; Humans; Male; Middle Aged; Platelet Count; Thromboxane B2